Time to recovery from malnutrition and its predictors among human immunodeficiency virus positive children treated with ready‐to‐use therapeutic food in low resource setting area: A retrospective follow‐up study

Abstract Background and Aim Malnutrition is a serious public health issue and a frequent impact of human immunodeficiency virus (HIV) infection, which raises the risk of morbidity and mortality in affected people. Despite the World Health Organization's (WHO) support for the use of ready‐to‐use therapeutic foods (RUTF) to treat malnutrition, research on the length of time it takes for children with HIV infection to recover from malnutrition and the factors that predict it is lacking, particularly Ethiopia. Methods An institution‐based retrospective follow‐up study was carried out in the Amhara regional state referral hospitals in Northern Ethiopia. From 2013 to 2018, a total of 478 children who received RUTF treatments were chosen using a simple random sampling technique. To calculate the likelihood of recovery and the median recovery period, incidence and Kaplan–Meier survival analyses were performed. The Cox regression model was used to identify predictors of time to recovery from malnutrition. The multivariable model only included variables with a p value below 0.2. While factors were deemed to be substantially linked with the outcome variable if their p value was less than 0.05. Results The median recovery duration was 5 months (95% confidence interval [CI] = 4–5 months), and the nutritional recovery rate was 64.64% (95% CI = 60.2–68.9). Moderate acute malnutrition (adjusted hazard ratio [AHR] = 4.60, 95% [CI] = 2.85–7.43), WHO clinical stage I (AHR = 4.01, 95% CI = 1.37–11.77), absence of opportunistic infection (AHR = 1.76, 95% CI = 1.19–2.61), haemoglobin (Hgb) count above the threshold (AHR = 1.36, 95% CI = 1.01–1.85) and family size of 1–3 (AHR = 2.38, 95% CI = 2.38–5.00) were significantly linked to rapid recovery from malnutrition. Conclusion In comparison to the period specified by the national guideline (3 months for moderate and 6 months for severe acute malnutrition), the median time to recovery was lengthy. Acute malnutrition, clinical stage, opportunistic infection, Hgb count, and family size were statistically associated with early recovery from malnutrition.

are the most prevalent types of malnutrition brought on by energy deficits. 2 Children's malnutrition is a significant public health issue in countries with low resources, such as Ethiopia. 3 It is also a crucial contributor to the progression of the disease and one of the main side effects of human immunodeficiency virus (HIV) infection and acquired immunodeficiency syndrome (AIDS). 4 The poor nutritional status of children has a negative effect on HIV-infected patients through compromised food intake, alterations in intermediary metabolism, and nutrient mal-absorption. 4 Furthermore, it decreases patients' levels of micronutrients necessary for the proper operation of acquired and innate immunity, which raises the risk of morbidity and mortality, increases the severity of disease, and delays recovery in HIV-infected children. 5 Malnutrition's impact on HIV patients is primarily observed in low-and middle-income nations. 6,7 According to a study conducted in Africa, malnutrition affects children with HIV at a rate of 42%. 8 Similarly, 60.2% of HIV-positive children in a research conducted in west Gojjam, Ethiopia, experienced malnutrition. 9 The nutritional condition of children with HIV infection is influenced by a variety of factors, including the child's sex, 10,11 age, 12 concomitant diseases such tuberculosis, oral ulcer, diarrhea, 13 and history of hospital admission. 14 To lessen the impact of malnutrition and enhance nutrition delivery services, Ethiopia has developed the National Nutrition Program. As part of an Outpatient Therapeutic Program employing ready-to-use therapeutic food (RUTF), a community-based preventative food and nutrition intervention is one method for enhancing the nutritional status of HIV/AIDS patients). 15 In the past, children with severe wasting, underweight, or both severe wasting and underweight received RUTF. Due to increased donor support, the clinical nutrition treatment program now accepts individuals with HIV and children with moderate acute malnutrition (MAM). 16 Children with MAM and severe acute malnutrition (SAM) who have a strong appetite and no medical issues are managed with RUTF. 12 Despite the availability of this medication, there are still many children with HIV who are malnourished. Additionally, the efficiency of RUTF and antiretroviral treatment (ART) therapies and their results have been studied in very few studies in Low and Middle-Income Countries. However, the studies looking at the start of ART among patients receiving RUTF concentrated on wasting state alone, and the relationship between the length of RUTF treatment and nutritional status has not yet been examined. Therefore, the purpose of this study is to evaluate how long it takes for HIV-positive children who received treatment in a resourcelimited context in Ethiopia to recover from malnutrition and the factors that influence it.

| Study design and setting
A retrospective follow-up study was carried out at ART clinics and referral hospitals in the Amhara regional states to determine the length of time it took for HIV-positive children enrolled in the RUTF treatment program from September 30, 2013, as well as the factors that predicted when they would recover from malnutrition. The Amhara regional state is located in Ethiopia's northern part. Five referral hospitals offer chronic HIV care (ART) services together with other services in the Amhara regional state. Around 2975 children had received ART follow-up in these hospitals at the time of data abstraction. The study was carried out in the four referral hospitals that were chosen.

| Sample size determination and sampling procedure
The sample size was determined by taking into account predictors from a prior study that were strongly related to the length of time it took for malnutrition to recover after RUTF treatment 17 using either STATA or Schoenfeld formula. 18

| Data collection methods and procedures
The patient follow-up cards, RUTF registration books, computerized information databases, and patient follow-up cards were all employed as data sources. Additional clinical records were gathered, including test results for biomarkers and any pertinent investigations.
The card number from the health management information system was utilized to identify specific patient cards. Patient cards were used to capture socio-demographic information, baseline, follow-up clinical data, and laboratory information. Data was collected from the start of RUTF to the end of follow-up time.

| Censored
Those who were not experiencing recovery from undernutrition until the end of the study, died before experiencing recovery within the study period, and lost follow-up before experiencing recovery within the study period by reason not related to the event were counted as censored. 19

| Children
A child is a person 18 years or younger unless national law defines a person to be an adult at an earlier age. 14

| The event of interest
The event of interest is recovery from malnutrition during the followup period.

| Incidence of recovery
The children were monitored for a minimum of 2 months and a maximum of 6 months, with a mean follow-up period of 4 months (SD ± 1 month). During follow-up, a total of 309 (64.64%) children recovered from malnutrition ( Figure 1).

| Time to recovery from malnutrition after the initiation of RUTF
In our study, the median recovery time from malnutrition was 5 months (95% CI = 4-5). The cumulative proportion of recovery was 0.6% at 2 months, 17.5% at 3 months, 49.5% and 78% at 5 and 6 months, respectively ( Figure 2). admission. According to this study, the problem could be that children weren't getting iron supplements even if they were anaemic.
Another result found in this study is that a family size greater than 7 members was considered a risk factor for prolonged nutritional recovery time, the main explanation behind could be that, as the family size increases the likelihood of sharing RUTF amongst family member increase as well as other nutritional supplementations and cares given for the child will decrease. This conclusion was reinforced by a qualitative study conducted in Addis Ababa, Ethiopia, which indicated that 1 in 3 patients share food with their children and other HIV-positive individuals with whom they have comparable health conditions simply because they are unable to avoid doing so due to their culture. 30

| LIMITATION OF THE STUDY
Certain types of information, such as laboratory results and therapies administered, were lacking for some of the patients since this study is a retrospective follow-up that is based on a review of routinely gathered data from four referral hospitals. There was no information on the availability of food in the home, dietary intake from other sources, food sharing among family members, or patient compliance for nutrition therapy, which may have tainted the outcomes of our predictive factor analysis.

| CONCLUSION
The finding of this study confirmed that the recovery rate from malnutrition was below the recommended national standard. Level of malnutrition, opportunistic infection, WHO clinical stage, Hgb count at admission, and household family size were associated with recovery time.

| RECOMMENDATION
The federal ministry of Health shall formulate regular and comprehensive nutritional screening programs among children living with HIV/AIDs to improve nutritional treatment outcomes.
Health care professionals shall screen for anemia and initiate

ACKNOWLEDGMENTS
Our gratitude goes to the University of Gondar and Ambo University for their invaluable support. We would like to thank all hospitals' Directors, the ART department, and triage members in each respective hospital as well as data collectors for their cooperation.

CONFLICTS OF INTEREST
The authors declare no conflicts of interest.

DATA AVAILABILITY STATEMENT
All data that support the findings of this study are available from the corresponding author upon request.

TRANSPARENCY STATEMENT
The lead author Martha kassahun Zegeye affirms that this manuscript is an honest, accurate, and transparent account of the study being reported; that no important aspects of the study have been omitted; and that any discrepancies from the study as planned (and, if relevant, registered) have been explained.